The Effect of Magnesium Supplementation on Vascular Calcification in CKD: A Randomized Clinical Trial (MAGiCAL-CKD).

SIGNIFICANCE STATEMENT: Magnesium prevents vascular calcification in animals with CKD. In addition, lower serum magnesium is associated with higher risk of cardiovascular events in CKD. In a randomized, double-blinded, placebo-controlled trial, the authors investigated the effects of magnesium supplementation versus placebo on vascular calcification in patients with predialysis CKD. Despite significant increases in plasma magnesium among study participants who received magnesium compared with those who received placebo, magnesium supplementation did not slow the progression of vascular calcification in study participants. In addition, the findings showed a higher incidence of serious adverse events in the group treated with magnesium. Magnesium supplementation alone was not sufficient to delay progression of vascular calcification, and other therapeutic strategies might be necessary to reduce the risk of cardiovascular disease in CKD. BACKGROUND: Elevated levels of serum magnesium are associated with lower risk of cardiovascular events in patients with CKD. Magnesium also prevents vascular calcification in animal models of CKD. METHODS: To investigate whether oral magnesium supplementation would slow the progression of vascular calcification in CKD, we conducted a randomized, double-blinded, placebo-controlled, parallel-group, clinical trial. We enrolled 148 subjects with an eGFR between 15 and 45 ml/min and randomly assigned them to receive oral magnesium hydroxide 15 mmol twice daily or matching placebo for 12 months. The primary end point was the between-groups difference in coronary artery calcification (CAC) score after 12 months adjusted for baseline CAC score, age, and diabetes mellitus. RESULTS: A total of 75 subjects received magnesium and 73 received placebo. Median eGFR was 25 ml/min at baseline, and median baseline CAC scores were 413 and 274 in the magnesium and placebo groups, respectively. Despite plasma magnesium increasing significantly during the trial in the magnesium group, the baseline-adjusted CAC scores did not differ significantly between the two groups after 12 months. Prespecified subgroup analyses according to CAC>0 at baseline, diabetes mellitus, or tertiles of serum calcification propensity did not significantly alter the main results. Among subjects who experienced gastrointestinal adverse effects, 35 were in the group receiving magnesium treatment versus nine in the placebo group. Five deaths and six cardiovascular events occurred in the magnesium group compared with two deaths and no cardiovascular events in the placebo group. CONCLUSIONS: Magnesium supplementation for 12 months did not slow the progression of vascular calcification in CKD, despite a significant increase in plasma magnesium. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov ( NCT02542319 ).

Long-term cardiovascular outcomes and temporal trends in patients diagnosed with ANCA-associated vasculitis: a Danish nationwide registry study.

OBJECTIVES: To examine long-term cardiovascular outcomes and temporal trends among patients with ANCA-associated vasculitis (AAV) using Danish nationwide registries. METHODS: Using a cohort design, we examined patients with granulomatosis with polyangiitis (ICD-10: DM31.3) and microscopic polyangiitis (ICD-10: DM3.17) in Denmark from 1996-2018. Hazard ratios (HRs) of cardiovascular outcomes were compared between patients with AAV and age and gender-matched controls. Counterfactual G-estimation of HRs was performed to estimate 5-year absolute risks. Temporal trends were obtained by grouping cohorts into evenly distributed tertiles according to inclusion year. RESULTS: A total of 2306 patients with AAV (median age: 62.9yrs, 52.6% male) were matched with 6918 controls. Median follow-up was 9.5yrs. Patients with AAV had a higher rate of ischaemic heart disease [HR 1.86 (1.62-2.15)], myocardial infarction [HR 1.62 (1.26-2.09)], coronary angiogram [HR 1.64 (1.37-1.96)], percutaneous coronary intervention [HR 1.56 (1.17-2.07)] and ventricular arrhythmias/implantable-cardioverter-defibrillator (ICD)-implantations [HR 2.04 (1.16-3.57)]. Similarly, an increased rate of heart failure [HR 2.12 (1.77-2.54)], deep vein thrombosis [HR 3.13 (2.43-4.05)], pulmonary embolism [HR 4.04 (3.07-5.32)], atrial fibrillation [HR 2.08 (1.82-2.39)], ischaemic stroke [HR 1.58 (1.31-1.90)] and in-hospital cardiac arrest [HR 2.27 (1.49-3.48)] was observed. The 5-year risk of all outcomes were significantly higher (excluding ventricular arrhythmia/ICD-implantations). For temporal trends among patients with AAV, a decreased 3-year risk of cardiovascular mortality was observed over time. CONCLUSIONS: Patients with AAV are at increased risk of heart failure, atrial-/ventricular arrhythmias, venous thrombotic events, ischaemic stroke and myocardial infarction. Furthermore, patients with AAV were more frequently examined with coronary procedures and underwent more coronary revascularizations. No temporal changes in ischaemic cardiovascular outcomes were observed, albeit the cardiovascular mortality has decreased over time.

Increased risk of cardiovascular disease preceding diagnosis of incident ANCA-associated vasculitis: a Danish nationwide study.

OBJECTIVE: To examine if patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV. METHODS: Using a nested case-control framework, patients with Granulomatosis with polyangiitis and Microscopic polyangiitis were identified through Danish Nationwide Registries from 1996-2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV-diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted Hazard Ratios (HRs) for major adverse cardiovascular events (MACE), ischemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischemic stroke, pericarditis, and ventricular arrhythmias/ICD-implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date. RESULTS: A total of 2371 patients with AAV (median age: 63yrs, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared to 3.8% (HR 3.05[2.48-3.75]) and 1.3% (HR 1.98[1.39-2.82]) of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: Any cardiovascular outcome (HR 10.73[7.05-16.32]) and MACE (HR 5.78[2.67-12.52]). In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA). CONCLUSIONS: AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance toward cardiovascular disease.

Cardiovascular mortality in patients with advanced chronic kidney disease with and without diabetes: a nationwide cohort study.

BACKGROUND: Cardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels. METHODS: In a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m2 between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort. RESULTS: We included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6-10.0) and 7.4% (95% CI 7.3-7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1-3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes. CONCLUSIONS: Diabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD.

Toward a Transportable Cell Culture Platform for Evaluating Radiotherapy Dose Modifying Factors.

The current tools for validating dose delivery and optimizing new radiotherapy technologies in radiation therapy do not account for important dose modifying factors (DMFs), such as variations in cellular repair capability, tumor oxygenation, ultra-high dose rates and the type of ionizing radiation used. These factors play a crucial role in tumor control and normal tissue complications. To address this need, we explored the feasibility of developing a transportable cell culture platform (TCCP) to assess the relative biological effectiveness (RBE) of ionizing radiation. We measured cell recovery, clonogenic viability and metabolic viability of MDA-MB-231 cells over several days at room temperature in a range of concentrations of fetal bovine serum (FBS) in medium-supplemented gelatin, under both normoxic and hypoxic oxygen environments. Additionally, we measured the clonogenic viability of the cells to characterize how the duration of the TCCP at room temperature affected their radiosensitivity at doses up to 16 Gy. We found that (78±2)% of MDA-MB-231 cells were successfully recovered after being kept at room temperature for three days in 50% FBS in medium-supplemented gelatin at hypoxia (0.4±0.1)% pO2, while metabolic and clonogenic viabilities as measured by ATP luminescence and colony formation were found to be (58±5)% and (57±4)%, respectively. Additionally, irradiating a TCCP under normoxic and hypoxic conditions yielded a clonogenic oxygen enhancement ratio (OER) of 1.4±0.6 and a metabolic OER of 1.9±0.4. Our results demonstrate that the TCCP can be used to assess the RBE of a DMF and provides a feasible platform for assessing DMFs in radiation therapy applications.

EDTAKI: a Nephrology and Public Policy Committee platform call for more European involvement in acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is an often neglected but crucial element of clinical nephrology. The aim of the Nephrology and Public Policy Committee (NPPC) of the European Renal Association-European Dialysis and Transplant Association is to promote several key aspects of European nephrology. One of the targets proposed by the NPPC was to advance European nephrology involvement in AKI. METHODS: We undertook a literature analysis to define the current position of European nephrology in the field of AKI compared with other regions and to determine how different European countries compare with each other. RESULTS: It appeared that vis-à-vis countries with a comparable socio-economic status (the USA, Australia, New Zealand and Canada), the European contribution was almost 50% less. Within Europe, Central and Eastern Europe and countries with a lower gross domestic product showed lower scientific output. Nephrologists contributed to less than half of the output. There was no trend of a change over the last decade. CONCLUSIONS: There is room to improve the contribution of European nephrology in the field of AKI. We propose a model on how to promote clinical collaboration on AKI across Europe and the creation of a pan-European nephrology network of interested units to improve clinical outcomes, increase nephrologist involvement and awareness outside nephrology and stimulate research on AKI in Europe. Accordingly, we also propose a list of research priorities and stress the need for more European funding of AKI research.

Increased risk of neonatal complications and infections in children of kidney-transplanted women: A nationwide controlled cohort study.

Information related to short- and long-term risks of children born to kidney-transplanted women remains limited. With the aim of investigating the risk of neonatal complications, and the short- and long-term risk of infections in offspring of kidney-transplanted women, all children born to kidney-transplanted women in Denmark from 1964 to 2016 were identified in a nationwide retrospective matched cohort study. A total of 124 children of kidney-transplanted women were identified and matched on gender, birth year, and number of siblings at birth 1:10 with children born to nontransplanted women identified in the Danish general population. Prevalence of low birth weight (37.9%, risk ratio [RR] = 12.61; 95% confidence interval [CI], 8.5-18.5), premature birth (46.0%, RR = 11.32; 95% CI, 8.1-15.7) and malformations (11.3%, RR = 1.98; 95% CI, 1.2-3.4) was increased in children of kidney-transplanted women compared with controls. Similarly, prevalence of hospitalization due to infection was increased during the first year of life (21.0%, RR = 1.94; 95% CI, 1.3-2.8), from age 1 to 5 (34.2%, RR = 1.89; 95% CI, 1.4-2.5), and overall (41.9%, RR = 1.67; 95% CI, 1.3-2.1). The risk of infection was also higher in children of kidney-transplanted mothers born preterm or with low birth weight compared with similar controls. In conclusion, risk of neonatal complications, malformations, and both early and late infection were increased in children born to kidney-transplanted women.

Increasing incidence and improved survival in ANCA-associated vasculitis-a Danish nationwide study.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) carries a high risk of morbidity and mortality, with outcomes modified by treatment and an incidence that may be increasing. We examined temporal changes in incidence and mortality during 2000-15 using nationwide healthcare registries. METHODS: Patients with incident AAV were identified using International Classification of Diseases Version 10 (ICD10) codes and grouped according to inclusion year (Period 1: 2000-04, Period 2: 2005-09, Period 3: 2010-15). Log link cumulative incidence regression adjusted for age, sex, renal function, cardiovascular disease, diabetes, hypertension and advanced disease severity were used to model survival. RESULTS: We identified 1631 patients (52% male), corresponding to an incidence of 18.5 persons/million/year (Period 1: 15.1, Period 2: 18.5, Period 3: 21.4). The slope of incident serologic ANCA testing was steeper than that of AAV (P = 0.002). Mean [standard deviation (SD)] age was 60.2 (16.7) years and mean (SD) follow-up was 6.8 (4.7) years. A total of 571 (35%) patients died (5-year mortality of 22.1%), with an absolute risk ratio (ARR) for Periods 2 and 3 compared with Period 1 of 0.80 [confidence interval (CI) 0.65-0.98, P = 0.031] and 0.39 (CI 0.31-0.50, P < 0.001). About 274 patients developed end-stage renal disease (ESRD) [16.8% (Period 1: 23.3%, Period 2: 17.6%, Period 3: 12.5%)], with ARR decreasing over time: Period 2 0.61 (CI 0.42-0.87, P = 0.007) and Period 3 0.57 (CI 0.39-0.83, P = 0.003). The overall risk of death associated with ESRD or chronic kidney disease was 1.74 (CI 1.29-2.37, P < 0.001) and 1.58 (CI 1.21-2.07, P < 0.001). CONCLUSIONS: Incidence of ANCA testing and AAV diagnosis increased over the test period. Falls over time in mortality and ESRD risk may relate to earlier diagnosis and changes in treatment practice.

Regional distribution and severity of arterial calcification in patients with chronic kidney disease stages 1-5: a cross-sectional study of the Copenhagen chronic kidney disease cohort.

BACKGROUND: Patients with chronic kidney disease (CKD) and arterial calcification are considered at increased risk of adverse cardiovascular outcomes. However, the optimal site for measurement of arterial calcification has not been determined. The primary aim of this study was to examine the pattern of arterial calcification in different stages of CKD. METHODS: This was an observational, cross-sectional study that included 580 individuals with CKD stages 1-5 (no dialysis) from the Copenhagen CKD Cohort. Calcification of the carotid, coronary and iliac arteries, thoracic and abdominal aorta was assessed using non-contrast multidetector computed tomography scans and quantified according to the Agatston method. Based on the distribution of Agatston scores in the selected arterial region, the subjects were divided into calcium score categories of 0 (no calcification), 1-100, 101-400 and > 400. RESULTS: Participants with CKD stages 3-5 had the highest prevalence of calcification and the highest frequency of calcium scores > 400 in all arterial sites. Calcification in at least one arterial site was present in > 90% of patients with CKD stage 3. In all five CKD stages prevalence of calcification was greatest in both the thoracic and abdominal aorta, and in the iliac arteries. These arterial sites also showed the highest calcium scores. High calcium scores (> 400) in all five arterial regions were independently associated with prevalent cardiovascular disease. In multivariable analyses, after adjusting for cardiovascular risk factors, declining creatinine clearance was associated with increasing calcification of the coronary arteries (p = 0.012) and the thoracic aorta (p = 0.037) only. CONCLUSIONS: Arterial calcification is highly prevalent throughout all five CKD stages and is most prominent in both the thoracic and abdominal aorta, and in the iliac arteries. Follow-up studies are needed to explore the potential of extracardiac calcification sites in prediction of cardiovascular events in the CKD population.

Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction.

AIMS: Guidelines differ in their recommendations on therapy to prevent gastrointestinal bleeding for patients treated with dual antiplatelet treatment (DAPT). We sought to investigate the effectiveness of proton pump inhibitors (PPIs) to prevent upper gastrointestinal (UGI) bleeding in patients using DAPT following myocardial infarction (MI) in relation to current European Society of Cardiology guidelines recommendations. METHODS AND RESULTS: We linked Danish nationwide registries to identify patients taking DAPT 7 days following hospital discharge for an acute MI, and excluded individuals on anticoagulation therapy. We used multiple Cox regression modelling, to compute average risk of UGI bleeding in relation to PPI use. The associated treatment efficacy was compared based on guideline risk assessment. We studied 46 301 patients on DAPT after MI. Only 35% of patients at higher risk of UGI bleeding received recommended treatment with a PPI based on the guideline criteria. The 1--year risk of UGI bleeding was 1.0% [95% confidence interval (CI) 0.9-1.1%] and 1.7% (CI 1.5-2.0%) for high-risk patients. Overall PPI compared with no therapy, was associated with a risk ratio for UGI bleeding of 0.62 (CI 0.48-0.77) corresponding to an absolute risk difference of 0.44% (CI 0.39-0.48%). Proton pump inhibitor therapy was associated with a similar absolute risk difference [0.47% (CI 0.43-0.51%)] for high-risk patients. CONCLUSION: Proton pump inhibitor therapy is used less than suggested by guidelines in patients treated with DAPT following MI and was generally associated with reduced risk of UGI bleeding. Considering the overall low risk of bleeding, more focus should be on identifying patients benefiting the most from PPI therapy.

Incidence of atrial fibrillation in different major cancer subtypes: a Nationwide population-based 12 year follow up study.

BACKGROUND: The prevalence of both atrial fibrillation (AF) and malignancies are increasing in the elderly, but incidences of new onset AF in different cancer subtypes are not well described.The objectives of this study were therefore to determine the incidence of AF in different cancer subtypes and to examine the association of cancer and future AF. METHODS: Using national databases, the Danish general population was followed from 2000 until 2012. Every individual aged > 18 years and with no history of cancer or AF prior to study start was included. Incidence rates of new onset AF were identified and incidence rate ratios (IRRs) of AF in cancer patients were calculated in an adjusted Poisson regression model. RESULTS: A total of 4,324,545 individuals were included in the study. Cancer was diagnosed in 316,040 patients. The median age of the cancer population was 67.0 year and 51.5% were females. Incidences of AF were increased in all subtypes of cancer. For overall cancer, the incidence was 17.4 per 1000 person years (PY) vs 3.7 per 1000 PY in the general population and the difference increased with age. The covariate adjusted IRR for AF in overall cancer was 1.46 (95% confidence interval (CI) 1.44-1.48). The strength of the association declined with time from cancer diagnosis (IRR0-90days = 3.41 (3.29-3.54), (IRR-180 days-1 year = 1.57 (CI 1.50-1.64) and (IRR2-5 years = 1.12 (CI 1.09-1.15). CONCLUSIONS: In this nationwide cohort study we observed that all major cancer subtypes were associated with an increased incidence of AF. Further, cancer and AF might be independently associated.

Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study.

BACKGROUND: We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011-2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. RESULTS: Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26-0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39-1.78), MI (HR: 0.45, 95% CI: 0.18-1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77-1.26). CONCLUSION: NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

Diabetes and risk of peripheral artery disease in patients undergoing first-time coronary angiography between 2000 and 2012 - a nationwide study.

BACKGROUND: The risk of peripheral artery disease (PAD) in patients with diabetes mellitus (DM) and coronary artery disease (CAD) is an important and inadequately addressed issue. Our aim is to examine the impact of DM on risk of PAD in patients with different degrees of CAD characterized by coronary angiography (CAG). METHODS: Using nationwide registers we identified all patients aged ≥18 years, undergoing first time CAG between 2000 and 2012. Patients were categorized into DM/Non-DM group, and further classified into categories according to the degree of CAD i.e., no-vessel disease, single-vessel disease, double-vessel disease, triple-vessel disease, and diffuse disease. Risk of PAD was estimated by 5-year cumulative-incidence and adjusted multivariable Cox-regression models. RESULTS: We identified 116,491 patients undergoing first-time CAG. Among these, a total of 23.969 (20.58%) had DM. Cumulative-incidence of PAD among DM patients vs. non-DM were 8.8% vs. 4.9% for no-vessel disease, 8.2% vs. 4.8% for single-vessel disease, 10.2% vs. 6.0% for double-vessel disease, 13.0% vs. 8.4% for triple-vessel disease, and 6.8% vs. 6.1% for diffuse disease, respectively. For all patients with DM, the cox-regression analysis yielded significantly higher hazards of PAD compared with non-DM patients with HR 1.70 (no-vessel disease), 1.96 (single-vessel disease), 2.35 (double-vessel disease), 2.87 (triple-vessel disease), and 1.46 (diffuse disease), respectively (interaction-p 0.042). CONCLUSION: DM appears to be associated with increased risk of PAD in patients with and without established CAD, with increasing risk in more extensive CAD. This observation indicates awareness on PAD risk in patients with DM, especially among patients with advanced CAD.

Risk of incident atrial fibrillation in patients presenting with retinal artery or vein occlusion: a nationwide cohort study.

BACKGROUND: The inter-relationships of atrial fibrillation (AF) to retinal vascular occlusions (whether retinal artery occlusion (RAO) or retinal venous occlusion (RVO)) remain unclear. It is unknown if a presentation of retinal artery or venous occlusions may indicate a new onset cardiac arrhythmia. To shed light on this association, we investigated the risk of new onset AF in patients with known RAO and RVO. METHODS: Patients with retinal occlusions from 1997 to 2011 were identified through Danish nationwide registries and matched 1:5 according to sex and age. Cumulative incidence and unadjusted rates of AF according to retinal vascular occlusions (i.e. RAO or RVO) were determined. Hazard ratios (HR) of AF according to retinal vascular occlusion were adjusted for hypertension, diabetes, vascular disease and prior stroke/systemic thromboembolism/transient ischemic attack. RESULTS: One thousand three hundred sixty-eight cases with retinal vascular occlusions were identified (median age 71.4 (inter quartile range (IQR); 61.2-79.8), 47.3% male). RAO constituted 706 cases (51.6%) and RVO 529 (38.7%). The rate of incident AF amongst all cases with retinal vascular occlusion was 1.74 per 100 person-years (95% confidence interval (CI), 1.47-2.06) compared to 1.22 (95% CI, 1.12-1.33) in the matched control group. The rate of AF in RAO was 2.01 (95% CI, 1.6-2.52) and 1.52 (1.15-2.01) in RVO. HRs of incident AF adjusted for cardiovascular comorbidities were 1.26 (95% CI; 1.04-1.53, p = 0.019) for any retinal vascular occlusion, 1.45 (95% CI; 1.10-1.89, p = 0.015) for RAO, and 1.02 (95% CI; 0.74-1.39, p = 0.920) for RVO. CONCLUSIONS: A new diagnosis of retinal vascular occlusion in patients without prior AF was associated with increased risk of incident AF, particularly amongst patients with RAO. Awareness of AF in patients with retinal vascular occlusions is advised.

Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis.

INTRODUCTION: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. METHODS: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23, sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance. RESULTS: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed. CONCLUSIONS: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged.

Renal Function and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation: An Observational Cohort Study.

BACKGROUND AND PURPOSE: We sought to determine the risk of stroke/thromboembolism and bleeding associated with reduced renal function in patients with atrial fibrillation and the risk of stroke and bleeding associated with warfarin treatment in specific estimated glomerular filtration rate (eGFR) groups. METHODS: We conducted a register-based cohort study and included patients discharged with nonvalvular atrial fibrillation from 1997 to 2011 with available eGFR. RESULTS: A total of 17 349 patients were identified with eGFR available at baseline. All levels of lower eGFR were associated with higher risk of stroke/thromboembolism and bleeding. Use of warfarin was associated with higher bleeding risk in all eGFR groups; hazard ratios 1.23 (95% confidence interval [CI], 0.97-1.56), 1.26 (95% CI, 1.14-1.40), 1.18 (95% CI, 1.07-1.31), 1.11 (95% CI, 0.87-1.42), 2.01 (95% CI, 1.14-3.54) in patients with eGFR ≥90, 60 to 89, 30 to 59, 15 to 29, and <15 mL/min per 1.73 m2, respectively. Use of warfarin was associated with lower risk of stroke/thromboembolism in patients with eGFR ≥15 mL/min per 1.73 m2; hazard ratios 0.57 (95% CI, 0.43-0.76), 0.57 (95% CI, 0.51-0.64), 0.48 (95% CI, 0.44-0.54), 0.60 (95% CI, 0.45-0.80) in patients with eGFR ≥90, 60 to 89, 30 to 59, and 15 to 29 mL/min per 1.73 m2, respectively. Use of warfarin was not associated with lower risk of stroke/thromboembolism in patients with eGFR<15 mL/min per 1.73 m2; hazard ratio 1.18 (95% CI, 0.58-2.40). CONCLUSIONS: In patients with atrial fibrillation, the risk of stroke and bleeding was associated with levels of renal function. Warfarin treatment was associated with higher risk of bleeding in all eGFR groups and lower risk of stroke in patients with eGFR≥15 mL/min per 1.73 m2.

Metformin-associated risk of acute dialysis in patients with type 2 diabetes: A nationwide cohort study.

Recent guidelines governing anti-diabetic medications increasingly advocate metformin as first-line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug-naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1-year risk of acute dialysis was based on g-standardization of cause-specific Cox regression models for acute dialysis, end-stage renal disease and death. One-year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1-121.3) and 142.7 per 100 000 (95% CI, 118.3-168.0) for sulphonylurea and metformin, respectively. The metformin-associated 1-year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9-88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06-2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin.

A Population- and Hospital-based Cross-sectional Study of Renal Function in Hidradenitis Suppurativa.

The chronic inflammatory skin diseases hidradenitis suppurativa (HS) and psoriasis have been linked to cardiovascular risk factors and the latter has also been linked to possible renal dysfunction. Since basement membrane thinning in the skin of HS patients has been described, we speculated whether similar basement membrane defects might occur in renal tissue. Our objective was to investigate a possible association between HS and renal dysfunction. We performed a hospital and population-based cross-sectional study using estimated Glomerular-Filtration-Rate (eGFR) to assess renal function. Thirty-two hospital individuals with HS, 430 population individuals with HS, and 20,780 population individuals without HS were (controls) identified. The age-, sex-, smoking-, BMI-, hypertension- and diabetes-adjusted analysis revealed a statistically significant higher eGFR for the hospital group with HS and a mean difference in eGFR of 6.81 (1.27-12.35) ml/min/1.73 m2 between the hospital group with HS and the population group without HS. The observed higher eGFR in the hospital group with HS indicates a possible association of HS and renal dysfunction.

Comparison of antiplatelet regimens in secondary stroke prevention: a nationwide cohort study.

BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent stroke associated with these three treatments. METHODS: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke and 1.47 (95% CI: 1.18-1.82) for bleeding. Clopidogrel versus acetylsalicylic acid yielded HRs of 0.69 (95% CI: 0.59-0.81) and 0.72 (95% CI: 0.55-0.96) for stroke and bleeding, respectively. The 1-year predicted risks associated with acetylsalicylic acid, the combination of acetylsalicylic acid and dipyridamole, and clopidogrel were 11.1 (95% CI: 10.2-12.2), 7.7 (95% CI: 7.3-8.3), and 8.0 (95% CI: 6.9-8.7) for ischemic stroke, respectively; while, the risks for bleeding were 3.4 (95% CI: 2.8-3.9), 2.4 (95% CI: 2.1-2.7), and 2.4 (95% CI: 1.9-2.9), respectively. CONCLUSION: Clopidogrel and the combination of acetylsalicylic acid and dipyridamole were associated with similar risks for recurrent ischemic stroke and bleeding; whereas acetylsalicylic acid was associated with higher risks for both ischemic stroke and bleeding. The latter finding may partially be explained by selection bias.

Sialolithiasis in horses: A retrospective study of 25 cases (2002-2013).

This study evaluated outcomes of surgical treatment of equine sialolithiasis, highlighting cases involving the proximal parotid salivary duct. Sialoliths in the proximal parotid duct were difficult to identify radiographically and more frequently associated with draining tracts and sialadenitis compared with sialoliths in the distal parotid duct. Ultrasonography confirmed the diagnosis of sialolithiasis in all cases in which there was no radiographic evidence of a sialolith. All cases of proximal parotid duct sialolithiasis required transcutaneous removal. A longer duration of illness was observed in cases of proximal parotid duct sialolithiasis compared with cases involving the distal parotid duct, and in cases requiring transcutaneous removal compared with cases requiring transoral removal. Recurrence of sialolithiasis was documented in 24% of cases, all of which were located in the distal parotid duct. The average time to recurrence was 2.8 years.

Sialolithiase chez les chevaux : une étude rétrospective de 25 cas (2002­2013). Cette étude a évalué les résultats du traitement chirurgical de la sialolithiase équine et a mis en lumière des cas touchant le canal salivaire parotidien proximal. Les sialolithes du canal de Sténon étaient difficiles à identifier par radiographie et sont plus fréquemment associés à des faisceaux de drainage et à la sialadénite par opposition à des sialolithes dans le canal de Sténon distal. L'échographie a confirmé le diagnostic de sialolithiase dans tous les cas où il y avait des preuves radiographiques d'un sialolithe. Tous les cas de sialolithiase du canal salivaire parotidien proximal ont exigé une ablation transcutanée. Une plus longue durée de la maladie a été observée dans les cas de sialothiase du canal salivaire parotidien proximal par opposition aux cas touchant le canal de Sténon distal et, dans les cas exigeant l'ablation transcutanée par opposition aux cas exigeant l'enlèvement transoral. La récurrence de la sialolithiase a été documentée dans 24 % des cas et ils étaient tous situés dans le canal salivaire distal. Le délai moyen avant la récurrence était de 2,8 ans.(Traduit par Isabelle Vallières).